. "Appendix A: Age-Related Shifts in Neural Circuit Characteristics and Their Impact on Age-Related Cognitive Impairments." The Aging Mind: Opportunities in Cognitive Research. Washington, DC: The National Academies Press, 2000.
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The Aging Mind: Opportunities in Cognitive Research
they cannot be replaced by the generation of new neurons. While it has been known for a long time from work in rodents that some neurogenesis occurs in the adult dentate gyrus (Altman and Das, 1965), it was demonstrated only recently that this also occurs in the nonhuman primate (Gould et al., 1999b) and in humans as well (Eriksson et al., 1998). In addition, while the functional status of the new neurons in the dentate gyrus is unclear, it has been demonstrated that they project to CA3 and thus may form normal connections (Hastings and Gould, 1999). Furthermore, the prevailing notion that the hippocampus is the only telencephalic region in which neurogenesis occurs has now been challenged by a report that neurogenesis occurs in the nonhuman primate neocortex, particularly in cortical regions that would presumably play a dominant role in learning, memory, and cognition (Gould et al., 1999c); however, these data on neocortex are presently controversial and will need to be expanded and replicated.
How are we to integrate the notion of new neurons into our prevailing attitudes regarding age-related functional decline and neurodegenerative disorders? While much work lies ahead, several interesting recent reports demonstrate the potential importance of neurogenesis to aging, at least with respect to the dentate gyrus. For one thing, neurogenesis in the dentate gyrus is decreased in aging (Kuhn et al., 1996). There are also positive influences on neurogenesis that may be exploited in preventing the age-related decrease in neurogenesis. The simple process of training animals on a learning task that requires the hippocampus enhanced neurogenesis and the viability of the new neurons in the dentate gyrus of rats (Gould et al., 1999a). Similarly adult mice living in an enriched environment have increased neurogenesis in the hippocampus (Kempermann et al., 1997). Moreover, increased experience and social interaction led to an enhancement of neurogenesis in the dentate gyrus of aged animals (Kempermann et al., 1998). Finally, simple physical exercise (e.g., running) increased cell proliferation in the adult mouse dentate gyrus (van Praag et al., 1999).
The potential for hormonal impact on these processes makes this issue even more relevant to aging. For example, estrogen has been demonstrated to stimulate a transient increase in neurogenesis in the dentate gyrus of the adult female rat (Tanapat et al., 1999). Furthermore, it was recently demonstrated that the level of neurogenesis typical of a young animal could be restored in an aged animal by decreasing the high levels of circulating corticosteroids that commonly occur in aged animals (Cameron and McKay, 1999). Thus, while it is not yet possible to fit these data on neurogenesis into the present context of aging and the neurobiological substrate for age-related functional decline, it is clear that this will be an area of intense investigation in the future and an area of paramount importance in aging research. It will be especially important to determine the quantitative extent of neurogenesis and the functional implications of adding neurons to the aged brain. Do the new neurons par-